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. 2009 Dec 15;180(12):1218-26.
doi: 10.1164/rccm.200901-0116OC. Epub 2009 Sep 17.

Maternal exposure to particulate matter increases postnatal ozone-induced airway hyperreactivity in juvenile mice

Richard L Auten  1 , Erin N Potts, S Nicholas Mason, Bernard Fischer, Yuhchin Huang, W Michael Foster
Affiliations

Maternal exposure to particulate matter increases postnatal ozone-induced airway hyperreactivity in juvenile mice

Richard L Auten et al. Am J Respir Crit Care Med. .

Retraction in

Abstract

Rationale: Epidemiologic studies implicate air pollutant exposure during pregnancy as a risk factor for wheezing in offspring. Ozone exposure is linked to exacerbations of wheezing in children.

Objectives: To determine if maternal pulmonary exposure to traffic-related particles during pregnancy augments ozone-induced airway hyperresponsiveness in offspring.

Methods: C57BL6 time-mated mice were given NIST SRM#1648 (particulate matter [PM]) 0.48 mg, saline vehicle, or no treatment by tracheal insufflation twice weekly for 3 weeks. PM exposure augmented maternal lung inflammation and placental TNF-alpha, Keratinocyte-derived cytokine (KC), and IL-6 (measured at gestation Day 18). After parturition, dams and litters were exposed to air or ozone 1 ppm 3 h/d, every other day, thrice weekly for 4 weeks. Respiratory system resistance in pups was measured at baseline and after administration of nebulized methacholine.

Measurements and main results: Ozone increased airway hyperresponsiveness, but the increase was greatest in pups born to PM-treated dams. Whole-lung TNF-alpha, IL-1beta, KC, IL-6, and MCP-1 were increased in ozone-treated pups, with the greatest increase in pups born to dams given PM. Airway epithelial mucous metaplasia estimated by periodic acid-Schiff Alcian blue staining was increased in ozone-exposed pups born to PM-treated dams. Alveolar development, determined by morphometry, and airway smooth muscle bulk, estimated using alpha-actin histochemistry, were unaffected by prenatal or postnatal treatment.

Conclusions: Maternal pulmonary exposure to PM during pregnancy augments placental cytokine expression and postnatal ozone-induced pulmonary inflammatory cytokine responses and ozone-induced airway hyperresponsiveness without altering airway structure.

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Figures

Figure 1.
Figure 1.
Bronchoalveolar lavage fluid (BALF) (A) leukocyte count and (B) differential from pregnant mice 24 hours after treatment with low (0.48 mg) or high (0.96 mg) doses of St. Louis particle suspension by orotracheal instillation. Data are mean ± SEM. *P < 0.05 vs. saline. PM = particulate matter; WBC = white blood cell count. Gray bars, macrophages; black bars, neutrophils.
Figure 2.
Figure 2.
Effects of maternal treatment on placental cytokines. Data are mean ± SEM; n = 6 per treatment group. *P < 0.001 vs. saline or air. PM = particulate matter.
Figure 3.
Figure 3.
Effects of maternal treatment on (A) pup birth weight (mean ± SEM), (B) litter size (bar = mean), (C) postnatal body weights in air and ozone-treated pups at postnatal Day 8, and (D) postnatal Day 28. Data are means from 25 to 30 pups (from three litters) per treatment group ± SEM. PM = particulate matter.
Figure 4.
Figure 4.
Effects of maternal treatments on whole lung cytokine concentrations in air- or ozone-exposed pups. Mean ± SEM; n = 4 to 5 per group. PM = particulate matter.
Figure 5.
Figure 5.
Effects of maternal treatment on total (Rtotal) or large airway (RNewtonian) resistance in (A) air- or (B) ozone-treated pups treated with increasing concentrations of nebulized methacholine (mean, 20–25 per group) ± SEM. +P < 0.05 vs. group born to air-treated dams; *P < 0.05 vs. group born to saline-treated dams. (C) Effects of maternal treatment on respiratory system compliance (mean ± SEM). PM = particulate matter.
Figure 6.
Figure 6.
Effect of maternal treatments on periodic acid-Schiff (PAS) glycoprotein staining of airway epithelium in air-exposed or ozone-exposed pups. Upper: PAS epithelial cell staining (arrowheads) in airways of juvenile mice from PM- and saline-treated dams and exposed postnatally to ozone or air are shown in representative photomicrographs (scale bar = 100 μm). Lower: Histogram of PAS scoring of large airways scored in 6 to 8 pups per group (line = mean). PM = particulate matter.
Figure 7.
Figure 7.
Effect of maternal treatment on (A) alveolar volume density (VD) and (B) alveolar surface density (Sv) in pups exposed to air or ozone. Data are mean ± SEM (n = 5–6 per group group). PM = particulate matter.
See this image and copyright information in PMC

Comment in

  • Findings of Research Misconduct.
    [No authors listed] [No authors listed] Fed Regist. 2019 Nov 7;84(216):60097-60098. Fed Regist. 2019. PMID: 37547121 Free PMC article. No abstract available.

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